(1) Field of the Invention
This invention relates to drug delivery apparatus, particularly, but not exclusively, nebulizers and dosimetric spacers.
(2) Description of the Related Art
Many different types of nebulizers are known for delivering medication directly into the lungs of a patient, usually for treatment of respiratory diseases. Nebulizers normally deliver medication in the form of droplets or a dry powder. In most nebulizers, atomization of the medicament into a stream of air occurs continuously, regardless of whether the patient is inspiring or expiring. However, the effect of continuous atomization is that a significant proportion of the medication is lost during expiration.
Commonly known nebulizers are either pneumatically operated from a compressed air source connected to the nebulizer which atomizes the liquid, or are ultrasonic nebulizers which use a piezoelectric crystal to atomize the liquid. More recently, a mesh-type nebulizer has been developed in which the medication is forced through a fine mesh in order to create droplets of the medication. A further type of nebulizer, or inhaler, is one which uses a piezoelectric vibrator together with an electro-static charge plate to fluidize and disperse a dry powder aerosol into an airstream. Such a nebulizer is disclosed in U.S. Pat. No. 5,694,920.
The optimum diameter of medication particles or droplets is about 1-5 microns. If the particles or droplets are bigger than this, they are likely to be impacted in the airway before they reach the lungs, but if they are smaller than one micron, they tend to be carried out of the lungs again on exhalation without sedimenting in the lungs.
Nebulizers and inhalers disperse the small particles of medication into an air stream, or stream of other gas, leading to a patient. References to the air which carries the medication entrained in it include other gases suitable for carrying the medication.
One known nebulizer analyses the pressure changes within the device during the first three breaths to determine an average shape of the breathing pattern. A timed pulse of atomization is commenced when starting subsequent inspirations such that atomization occurs for the first 50% of the inspiration. This is illustrated in FIG. 1 where the breathing pattern and pulse are superimposed. This is effective in reducing the loss of medication during exhalation to about 3%. FIG. 1 shows the breaths in a graph of flow rate against time. When the treatment is commenced, a patient breathes in and out three times through the nebulizer before treatment commences. The first three breaths are measured so that the timed pulse of atomization occurs for 50% of the average time of inhalation. The duration of inhalation is indicated as T1, T2 and T3. These timed periods are averaged, and divided by two in order to determine the pulse length for the next fourth breath where treatment starts. For each subsequent breath, the duration of the pulse of atomization is determined by summing the time period of inhalation of the previous three breaths, dividing by three to obtain an average and dividing by two. The dose administered to the patient is directly proportional to the duration of the pulse of atomization, and so the period of atomization is summed, and the atomizer is switched off, or indicates that the patient should stop once the dose administered to the patient reaches the amount of medication prescribed for that treatment.
Other nebulizers are known in which the timed pulse of atomization is fixed to be other than 50% of the duration of inspiration. However, in these other nebulizers, the pulse length must be set for each patient by the clinician. Many of the nebulizers are, therefore, suitable only for use in a controlled environment, such as a hospital. The setting of the pulse length for each patient means that most nebulizers are not suitable for a patient to use at home.
Reference is made to our co-pending International Patent Publication No. WO 97/48431, the disclosure of which is incorporated by reference herein in its entirety as if set forth at length. FIGS. 2 and 3 of this application show the nebulizer which is disclosed in the above co-pending Patent application. Referring to FIG. 2, a mouthpiece 1 is shown through which a patient inhales in the direction of arrow 2. Below the mouthpiece 1 is a removable atomizing section 3 which, in turn, rests on a base 4.
The base 4 is shown in more detail in FIG. 3. Referring to FIG. 3, the base 4 includes an inlet 5 through which air is supplied under pressure from a compressor (not shown). The pressurized air is led via a tube 6 to a manifold 7 which controls the flow of pressurized air to an air outlet 8 which directs air into the atomizing section 3 shown in FIG. 2. The base 4 also includes a pressure sensor 9 which detects the pressure within the atomizing section 3 via a port 10.
Referring again to FIG. 2, air under pressure passes through the air outlet 8 of the base 4 and is conducted through a tubular post 11 to an atomizer nozzle 12 out of which the air issues under pressure. A deflector 13 is located in the path of the pressurised air issuing from the nozzle 12 so that the pressurized air is deflected laterally so as to pass beneath a baffle 14. The passage of the pressurized air across the top of the tubular post 11 causes medication 15 to be drawn up between the outer surface of the tubular post 11 and the inner surface of a sleeve 16 which surrounds the tubular post 11. The medication 15 is atomized in the stream of air, and carried away in the stream of air below the rim of the baffle 14 and up through the mouthpiece 1 to a patient.
The pressure sensor 9 in the base 4 monitors the breathing pattern of a patient, and on the basis of the breathing pattern, the manifold 7 is controlled to supply pressurized air to the atomizing section 3 only during the first 50% of an inhalation phase.
While a particular type of nebulizer is described above, the present application is suitable for application to any type of nebulizer.
The invention also relates to other drug delivery apparatus, such as spacers in which a dose of a drug in droplet or powder form is released into a spacer chamber or holding chamber from which the patient inhales. These are most appropriate for elderly patients or children who have difficulty in using a multi-dose inhaler or dry powder inhaler, for example, because they have trouble coordinating the release of the drug with the beginning of inhalation, or because their inhalation flow rates are too small. For example, spacers are disclosed in International patent publication number WO 96/13294, the disclosure of which is incorporated by reference herein in its entirety as if set forth at length.
According to a first aspect of the present invention, a drug delivery apparatus comprises a drug delivery device for selectively delivering medication-laden air or air not carrying any medication to a patient for inspiration, wherein medication-laden air is selected to be delivered in pulses; a sensor for monitoring a patient""s breathing pattern; and a controller for controlling the said delivery device to deliver the medication in pulses, wherein the length of the pulses, and their proportion of the inspiratory phase of the breathing pattern are varied by the controller depending on the breathing pattern monitored by the sensor.
Preferably, the drug delivery apparatus is a nebulizer in which atomization occurs in pulses. It could, alternatively be a dosimetric spacer in which drug-laden air or gas is released from a holding chamber in pulses.
According to a second aspect of the invention, a method for determining the duration of a pulse during which medication-laden air is delivered to a patient during inspiration comprises:
(i) measuring the tidal volume of a patient;
(ii) measuring the duration of inspiration of a patient;
(iii) storing an estimate of the volume of a patient""s upper airway; and
(iv) calculating the duration of the pulse on the basis of the measured tidal volume of the patient, the measured duration of inspiration and the stored estimated volume of the patient""s upper airway.
In this document, the upper airways of a patient are the mouth and trachea, and where a nebulizer is used, preferably include the volume of the nebulizer chamber.
The determination of the length of pulse enables the proportion of the inhalation time during which atomization occurs to be extended above 50% towards 100%. This will result in the patient receiving their treatment in a shorter time, since it will take fewer breaths to deliver the required dose of medication. However, there is no point in continuing delivering the medication into air which is inhaled by the patient at the end of his or her inspiratory phase (the xe2x80x98end volumexe2x80x99), since it will remain in the upper airways. The medication which does not go beyond the upper airways will be wasted when the patient exhales.
Thus, the invention according to the first and second aspects enables a pulse to be generated which is longer than 50% but which stops before the end volume of inspiration begins. Another advantage of this invention is that a patient""s adherence to the treatment regime will be much improved if the length of treatment is reduced.
In addition, the invention allows automatic optimization of the pulse length without it needing to be set by a clinician. This means that the pulse length will automatically be adapted to each patient on the basis of the patient""s breathing pattern at the time the medication is being administered. Thus, a nebulizer or other drug delivery apparatus may be used by the patient outside of the controlled environment of a hospital, and may be used at home. In addition, it is possible for the apparatus to indicate when a dose has been administered without the patient needing to count the number of breaths which he or she has taken.
According to the preferred embodiment, the tidal volume measuring device includes a peak flow detector for measuring a patient""s peak flow, and a tidal volume predictor for calculating the tidal volume on the basis of the peak flow measured by the peak flow detector, and the duration of inspiration measured by the timer.
Some or all of the values used in the calculations are mean values derived from a number of earlier measurements of each breathing pattern of the patient. For example, the patient will start inspiration through the apparatus, and the medication will not be delivered during the first three breaths. The first three breaths are analysed by recording the duration of inspiration, and the peak flows during inhalation as are required to determine the duration of a pulse of atomization. Delivery of the medication takes place on the fourth and subsequent breaths, in each case the values in the calculations are derived from a number of earlier measurements of the inspiration phase of a patient, in this case the previous three inspiratory phases.
Preferably, where the apparatus is a nebulizer, the atomization is caused by a stream of gas under pressure passing through the nebulizer and sourced from a gas supply means. This gas is normally air, and the source is preferably a compressor operating together with an accumulator. During atomization, gas from the accumulator is used to atomize the medication, and the compressor generates air under pressure to fill the accumulator.
If a patient""s inspiration is very long, the accumulator may be caused to be emptied, thereby disrupting atomization. The atomizer, therefore, preferably includes a limiter for limiting the duration of the pulse so as to maintain the accumulator in a state where it is always under some pressure. In addition, the accumulator may include a valve which, when the accumulator is full, vents gas to atmosphere thereby preventing it from becoming dangerously full. It is often preferable to maintain the compressor in operation all the time and to vent excess air to atmosphere rather than to switch the compressor on and off.
According to a third aspect of the present invention, a drug delivery apparatus comprises a tidal volume predictor for predicting the tidal volume of a patient, including a detector for measuring a patient""s peak flow, a timer for measuring the duration of inspiration, and a tidal volume calculator for calculating the tidal volume on the basis of the peak flow from the peak flow detector, and the duration of inspiration measured by the timer.
According to a fourth aspect of the invention, a method of predicting the tidal volume of a patient comprises:
(i) measuring a patient""s peak flow;
(ii) measuring the duration of inspiration of a patient; and
(iii) calculating the tidal volume on the basis of the measured peak flow, and the measured duration of inspiration of the patient.
Measuring the patient""s respiratory volume (tidal volume) has previously involved continually monitoring the patient""s inspiratory flow, typically every ten milliseconds. The flow rate is integrated over the duration of inspiration to determine the inspiratory volume. However, the third and fourth aspects of the invention determine the tidal volume of a patient much more simply. This invention reduces the amount of data processing which is required, thereby reducing the cost of the overall nebulizer. The peak flow is much simpler to measure, and can be used more simply in a calculation to determine the tidal volume.
According to a fifth and preferred embodiment, a nebulizer comprises apparatus for determining the duration of a pulse of atomization during inspiration, the apparatus including a tidal volume measuring device for measuring the tidal volume of a patient, a timer for measuring the duration of inspiration, an estimate storage device for storing an estimate of the volume of a patient""s upper airway, and a calculator for calculating the duration of the pulse on the basis of the tidal volume measured by the tidal volume measuring device, the duration of inspiration measured by the timer, and the stored estimated volume of a patient""s upper airway from the storage device.